Key result
Endothelin-receptor antagonists significantly reduced albuminuria (SMD 0.66; 95% CI 0.56-0.76) but increased the risk of cardiovascular and other serious adverse events compared with placebo.
Why the study?
Do endothelin-receptor antagonists reduce albuminuria and improve clinical outcomes in patients with diabetic nephropathy?
Meta-Analysis (n=2,034)
Do endothelin-receptor antagonists reduce albuminuria and improve clinical outcomes in patients with diabetic nephropathy?
While endothelin-receptor antagonists effectively reduce albuminuria in diabetic nephropathy, their clinical utility is limited by a significantly increased risk of cardiovascular and other serious adverse events.
Reduces albuminuria but increases cardiovascular events; challenges routine use in diabetic nephropathy and supports trials of safer agents.
AIM: Endothelin-receptor antagonists may be a novel therapeutic strategy for diabetic nephropathy, but their use remains controversial. This meta-analysis seeks to evaluate the effectiveness and safety of endothelin-receptor antagonists for patients with diabetic nephropathy. METHODS: Literature reviews of the PubMed, EMBASE and CENTRAL databases were conducted to identify randomized controlled trials (RCTs) comparing endothelin-receptor antagonist treatment with placebo in patients with diabetic nephropathy. Quality assessment was performed by using the Cochrane Handbook's tools for assessing risk of bias; meta-analysis was conducted by RevMan 5.3. RESUTLS: Five RCTs (n=2034 patients) were included for analysis. Compared with placebo, endothelin-receptor antagonists showed significant benefits for lowering albuminuria (five trials, n=2034 patients; SMD 0.66 95% confidence interval (CI) 0.56 to 0.76), but there was no significant difference in the risk of death (two trials, n=1674 patients; RR 1.49 95% CI 0.81 to 2.76). In addition, risk of cardiovascular events and other serious adverse events were significantly higher in the endothelin-receptor antagonists group than the placebo group (four trials, n=1956 patients; RR 1.45 95% CI 1.07 to 1.97; five trials, n=2034 patients; RR 1.32 95% CI 1.10 to 1.58). CONCLUSION: Endothelin-receptor antagonists can reduce albuminuria in patients with diabetic nephropathy, although use resulted in more serious adverse events compared with placebo. There is a potential need for further RCTs, which has larger sample size and longer duration.
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Yuan et al. (2015) conducted a meta-analysis in Diabetic nephropathy (n=2,034). Endothelin-receptor antagonists vs. Placebo was evaluated on Albuminuria (SMD 0.66, 95% CI 0.56 to 0.76). Endothelin-receptor antagonists significantly reduced albuminuria (SMD 0.66; 95% CI 0.56-0.76) but increased the risk of cardiovascular and other serious adverse events compared with placebo.
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